Progesterone is bound specifically and with high affinity by a cytoplasmic receptor in the uterus. The progesterone-receptor complex then leaves the cytoplasm and enters the nucleus to initiate the biological effects of progresterone. Progesterone action depends on a continued supply of cytoplasmic receptor. The progesterone receptor in the cytoplasm can be replenished by the release of "used" recepto from the nucleus, or the new synthesis of receptor, or both. Progesterone is metabolized in uterine nuclei to 5 alpha-pregnance- 3, 20-dione, whose affinity for the cytoplasmic receptor is not as great as that of progesterone. The affinity of pregnanedione for the nuclear receptor may also be low, so that the used receptor may be released and recycled. The synthesis of the cytoplasmic progesterone receptor and the metabolism of progesterone in uterine nuclei are both increased by estrogen. We will investigate the possibility of a relationship between progesterone metabolism in uterine nuclei and the replenishment of the cytoplasmic receptor during progesterone action.